The Carolina CCNE is focused on improving cancer disease control and management by utilizing exciting new and cutting edge nanotechnologies, developed from our first CCNE efforts,. Our efforts will work to improve the quality and duration of life and disease outcome for cancer patients by enhancing treatment and early detection. We propose five projects in two major areas as follows: Nano-Particle Based Biological and Chemotherapy includes Project 1: PRINT Nanoparticles: "Calibration Quality" Nano-tools for Studying Particle Biodistribution, Project 2: Ras pathway siRNA in Lung Cancer, and Project 3: Translational Nanosystems Chemotherapy in Lung Cancer. Carbon Nanotube Based Radiation Therapy and Early Detection include Project 4: Compact Micro Beam Radiation Therapy in Brain Cancer and Project 5: Digital Breast Tomosynthesis System. The proposed nanoparticle science is primarily focused on targeted delivery of biological (siRNA) and chemotherapy to cancer cells. A key basic science question we will address is the implications of nanoparticle size, shape and modulus in accessing various tissues in the body. This question can effectively be answered by the UNC-developed PRINT technology, which features exquisite control over particle properties and will result in the establishment of BioMaps for nanoparticle delivery. Two additional nanoparticle-based projects will deliver biological and chemotherapy in a targeted fashion to lung cancer, with four distinct nanoparticle types that are capable of carrying multiple payloads. We will establish the first direct comparison of efficacy and toxicity of these various approaches against the equivalent of clinical standard of care in sophisticated murine cancer models. With carbon nanotube-based field emission X-ray technology, a new compact microbeam radiation therapy source is proposed that will deliver high intensity and spatially distributed radiotherapy to high grade gliomas and other brain cancers. Lastly, a carbon nanotube-based clinic-ready breast tomosynthesis imaging device is proposed that would advance early detection and characterization of breast abnormalities, and help to distinguish cancer from benign disease. We believe that developing these technologies and preparing them for clinical trials will help in realizing the promise of nanotechnology in cancer care and positively impact the lives of cancer patients. Public Health Relevance: Nanotechnology can be part of an improved cancer management effort. The need for targeted delivery systems, capable of carrying multiple and varied payloads, coupled with early detection, is a prerequisite for efficient therapy and reduced toxicity leading to improved outcomes.